State-of-the-Art Small Animal PET/CT Instrumentation Yale University PET Center The goal of this shared instrumentation proposal is to expand the capabilities of the Yale Positron Emission Tomography (PET) Center by the acquisition of a state-of-the-art small animal PET/CT scanner for rodent research studies. PET imaging provides a non-invasive method to detect and examine biochemical processes and physiological functions in the living body. Through the use of specific radiolabeled molecules, state-of-the- art scanning equipment, and the techniques of tracer kinetic modeling, quantitative measurements of a wide range of physiological functions can be assessed in clinical and pre-clinical populations. PET has broad applications in the areas of oncology, cardiology, neurosciences, metabolic disorders, inflammation, drug delivery, and others. The goal of this proposal is to leverage the Yale PET Center's expertise in radiochemistry and quantitative PET imaging from our existing PET-only scanners and to expand the use of PET/CT in rodent research studies, as part of a translational arm to human PET/CT studies. We have chosen the proposed PET/CT system with large axial field-of-view, high sensitivity and resolution, and including measurement of photon depth of interaction. When these PET instrumentation characteristics are combined with a CT scanner, the system can provide ideal characteristics for rodent research studies of Yale investigators. The need for a combined PET/CT is self-evident for most small animal oncology research, which requires simultaneous anatomical localization of tumor uptake. Work in diabetes requires combined PET/CT for pancreas measurements of beta cell function, and cardiovascular studies require combined PET/CT to correlate CT- based anatomical and functional measures with PET physiological measurements. The need for combined PET/CT is of even greater importance in research studies using novel radiopharmaceuticals, where the interpretation of the spatial localization of a new tracer cannot be performed without high-resolution anatomical data. The proposed system will support NIH-funded investigators in the Departments of Biomedical Engineering, Cardiology, Diagnostic Radiology, Internal Medicine, Medical Oncology, Obstetrics and Gynecology, Neurology, Psychiatry, and Therapeutic Radiology. Enhanced utilization of novel radiopharmaceuticals and PET/CT imaging will lead to a better understanding of biochemical processes involved in cardiac disease, cancer, metabolic disorders, neuropsychiatric disorders, and others, which in turn will lead to the development of new or improved treatment for these diseases. Together, these applications hold tremendous potential to improve the health of the general public.